This study is positioned to identify and characterize the pathological and physiological factors associated with IC/PBS and their relationship with RCPS. It offers a novel opportunity to examine the genetic and common environmental contributions to IC/PBS phenotypes. Our multidisciplinary approach will expand knowledge of the underlying genetic, environmental, and neurobiological factors that promote IC/PBS and its primary symptom of pain. One major strength of this project is that it addresses all 3 MAPP RFA Research Priorities. Our primary objective is to comprehensively investigate UCPPS disease phenotypes. As we examine the demographic characteristics, IC/PBS symptoms, clinical features (e.g., symptoms of FM, IBS, and CFS), psychiatric symptoms, and psychosocial and functional status in Stage 1, we also will address the epidemiology of IC/PBS. In Stage 2 we conduct a deep phenotyping investigation of the IC/PBS physical/anatomical and physiological characteristics. An important aspect of these studies is the identification and characterization of pathological and physiological associations between IC/PBS and related RCPS, such as FM and CFS. Stage 2's emphasis on pathophysiology in a uniquely valuable small cohort, incorporates a basic/translational science component. Specifically, we will collect specimens to examine neural upregulation manifested as urothelial dysfunction for Project 3 (an organ-system approach) to complement our assessment of central sensitization and the HPA axis changes (a systemic approach).